Epothiolones are macrolide compounds that find utility in the pharmaceutical field. For example, epothilones A and B having the structures: may be found to exert microtubule-stabilizing effects similar to paclitaxel (TAXOL®) and hence cytotoxic activity against rapidly proliferating cells, such as tumor cells or other hyperproliferative cellular diseases. See, Hofle et al., Angew. Chem. Int. Ed. Engl., Vol. 35, No. 13/14, 1567-1569 (1996); WO93/10121 published May 27, 1993; and WO97/19086 published May 29, 1997.
Derivatives and analogs of epothilones A and B have been synthesized and may be used to treat a variety of cancers and other abnormal proliferative diseases. Such analogs are disclosed in Hofle et al., Id.; Nicolaou et al., Agnew. Chem. Int. Ed. Eng., Vol.36, No. 19, 2097-2103 (1997); and Su et al., Agnew. Chem. Int. Ed. Engl., Vol. 36, No. 19, 2093-2097 (1997). In some instances, epothilone derivatives have demonstrated enhanced properties over epothilones A and B. The present invention is concerned with the discovery that certain epothilone derivatives may be utilized to treat cancers that have demonstrated resistance to other chemotherapeutic agents, such as oncolytic agents of the taxane family of compounds.